Our long-term goal is to understand the mechanisms which control cell proliferation. The major objective is to understand the mechanism of action of epidermal growth factor (EGF) and other molecules which interact with EGF-receptors and modulate the activity of EGF. We also intend to improve the biophysical methods which we are now using and to develop new ones, which will enable us to study problems requiring more sensitive and sophisticated techniques. Our project is divided into five major directions of research. 1. Detailed analysis of the mechanism of EGF-induced receptor clustering. Various biophysical and biochemical approaches will be used to explore the process of EGF-induced receptor clustering and subsequent internalization. 2. Analysis of the mode of action of EGF with monoclonal antibodies directed against various domains of the receptor molecule. 3. Isolation and purification of EGF receptor with monoclonal antibodies and cloning the genes of the receptor molecule. 4. Determination of the cellular proteins which are phosphorylated by the EGF-sensitive kinase and investigation of the role of phosphorylation in the induction of the mitogenic signal. 5. Development of computer-enhanced video microscopy system which will increase the sensitivity and versatility of our approach.